chr6-20869862-T-C

Variant names:

• chr6-20869862-T-C
• rs9350294
• NM_017774.3:c.742+23684T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_017774.3(CDKAL1):​c.742+23684T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,984 control chromosomes in the GnomAD database, including 26,058 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.57 (26058 hom., cov: 31)
• Consequence: CDKAL1 NM_017774.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.405
• Publications: 6 publications found

Genes affected

CDKAL1 (HGNC:21050): (CDK5 regulatory subunit associated protein 1 like 1) The protein encoded by this gene is a member of the methylthiotransferase family. The function of this gene is not known. Genome-wide association studies have linked single nucleotide polymorphisms in an intron of this gene with susceptibilty to type 2 diabetes. [provided by RefSeq, May 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.689 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017774.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	NM_017774.3	MANE Select	c.742+23684T>C		intron	N/A	NP_060244.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKAL1	ENST00000274695.8	TSL:1 MANE Select	c.742+23684T>C		intron	N/A	ENSP00000274695.4
	CDKAL1	ENST00000378610.1	TSL:2	c.742+23684T>C		intron	N/A	ENSP00000367873.1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86783 AN: 151866 Hom.: 26049 Cov.: 31

Gnomad AFR AF: 0.383

Gnomad AMI AF: 0.798

Gnomad AMR AF: 0.569

Gnomad ASJ AF: 0.618

Gnomad EAS AF: 0.709

Gnomad SAS AF: 0.582

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.535

Gnomad NFE AF: 0.642

Gnomad OTH AF: 0.551

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.571 AC: 86839 AN: 151984 Hom.: 26058 Cov.: 31 AF XY: 0.580 AC XY: 43056 AN XY: 74266

African (AFR) AF: 0.383 AC: 15899 AN: 41466

American (AMR) AF: 0.568 AC: 8669 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.618 AC: 2141 AN: 3464

East Asian (EAS) AF: 0.708 AC: 3661 AN: 5170

South Asian (SAS) AF: 0.583 AC: 2808 AN: 4816

European-Finnish (FIN) AF: 0.756 AC: 7963 AN: 10534

Middle Eastern (MID) AF: 0.541 AC: 159 AN: 294

European-Non Finnish (NFE) AF: 0.642 AC: 43646 AN: 67962

Other (OTH) AF: 0.552 AC: 1167 AN: 2114

Alfa AF: 0.618 Hom.: 43310

Bravo AF: 0.549

Asia WGS AF: 0.617 AC: 2147 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.55
PhyloP100		0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs9350294; hg19: chr6-20870093;